571
The Reaction of Acyl Halides with Organotin Hydrides. The Mechanism of Aldehyde ForrnationlS2 Henry G. Kuivila3 and Edward J. Walsh, Jre4 Contribution f r o m the Department of Chemistry, University of New Hampshire, Durham, New Hampshire, and the Gates and Crelfin Laboratories, California Institute of Technology, Pasadena, California. Received August 12,1965 Abstract: Acid chlorides and acid bromides react with organotin hydrides to yield aldehydes and esters. The distribution of the two products depends on electronic and steric effects of R and the nature of X in RCOX. A freeradical mechanism for aldehyde formation is indicated by free-radical catalysis, fragmentation of the acyl radicals postulated as intermediates, and the effect of R on the reactivities of acid chlorides. The Hammett p value for the reaction of tri-n-butyltin radicals with substituted benzoyl chlorides is 2.6 in m-xylene, 2.7 in o-dichlorobenzene, and 4.0 in methyl acetate.
0
rganotin hydrides have been found to react with a variety of organic functional groups including halide^.^,^ The reduction of alkyl halides (eq. l), in which Sn* is a trisubstituted tin group, has been studied with regard to scope and mechanism.6 R-X
+ Sn*-H +R-H + Sn*-X
(1)
van der Kerk, Noltes, and Luijten' reported that benzaldehyde was obtained from the reduction of benzoyl chloride with triphenyltin hydride (eq. 2). Kuivila* found that when 1 mole of tri-n-butyltin hy(C&&SnH
+ CsHsCOCl + C6HsCHO + (CeHs)&lCl
H I CHz-C-Cl
I
CHKOCl
+ Sn*H
I --f
\
I
I
/
Results and Discussion When an acid chloride is mixed with tri-n-butyltin hydride at room temperature, an exothermic reaction frequently results. The reaction is usually complete within 20 hr. Our results show that formation of the expected aldehyde (eq. 4) is usually accompanied by formation of ester (eq. 5 ) . The relative yields of
+ RCOCl +RCHO + Sn*C1 RCOOCHzR 2SnH + 2RCOC1+
Sn*H
(2)
dride was added to 1 mole of succinyl dichloride, the only product isolated was y-chloro-y-butyrolactone (eq. 3, Sn* = (n-C4H9)3Sn),and when phthalyl dichloride was reduced under the same conditions with 2
CHzCOC1
hydride, with or without solvent, gave benzyl benzoate as the only product.
(5)
ester and aldehyde are dependent upon the acid chloride used, the experimental conditions employed, and the hydride used. Our results on the reduction of several acyl halides are presented in Table I. Table I. The Reaction of Acyl Halides with Tri-n-butyltin Hydride Neat and in Solution (0.63 M ) at Ambient Temperaturesn
0 +Sn*Cl
(3)
CH2-C
\.
(4)
R
0
moles of the hydride a 5 5 % yield of phthalide was isolated. Since then we have reported5 that the reduction of benzoyl chloride with tri-n-butyltin hydride in ether provided a 54% yield of benzaldehyde but that the major product was benzyl benzoate in the absence of a solvent. Recently, Kupchik and Kieselg have reported that the reduction of benzoyl chloride with triphenyltin (1) Th's research was supported in part by the National Science Foundation, Grant NSF-G-10,000, to the University of New Hampshire. (2) Presented at the 148th National Meeting of the American Chemical Society, Chicago, Ill., Sept. 1964. (3) (a) This work was begun during the tenure of a John Simon Guggenheim Memorial Foundation Fellowship at the California Institute of Technology, 1959; (b) author to whom inquiries should be addressed: Department of Chemistry, State University of New York at Albany, Albany, N. Y. (4) U. S. Public Health Service Predoctoral Fellow, 1962-1964. ( 5 ) H. G. Kuivila, Advan. Organomefal. Chem., 1, 47 (1964), and references therein. (6) L. W. Menapace and H. G. Kuivila, J. Am. Chem. Soc., 86, 3047 (1964). (7) G. J. M. van der Kerk, J. G. Noltes, and J. G. A. Luijten, J. Appl. Chem., 7, 356 (1957). (8) H. G. Kuivila, J . Org. Chem., 25, 284 (1960). (9) E. J. Kupchik and R. J. Kiesel, [bid., 29, 3690 (1964).
RCOCl CH3 G H5 n-C4H9 iGH7 t-CaH9 PhCH2 Ph Ph3Ce GHsO PhCHzO RCOBr GHs Ph
Yield (neat), % RCOzRCHO CHzR
. . .b
5
95 87"
19 36 56
81 64 33
65
35
95 61
. . .b
79 99
Solvent
Yield (soh), % RCOzRCHO . CH2R
DMBd MeOAc (n-C4Hs)sSnC1 DMB DMB
75 90 27 91 52
25 10 73 9 48
CBHSCH~
55
45
m-Xylene
90
...b
DMB
60
40
. . .b 21
. . .b
All yields reported in this table, except those noted, have been determined by g.1.c. analysis. None observed. c 80% by isolation. d 2,3-Dimethylbutane. e Yield based on isolation.
Ethyl and benzyl chloroformates are notably unreactive. The former was not completely reduced in 5 weeks at ambient temperature and gave ethyl formate as the only product. The latter was completely reduced in about 2 weeks and yielded only benzyl formate and fragmentation products (see below).
Kuivila, Walsh Aldehyde Formation in Acyl Halide-Organotin Hydride Reactions
512
The two acid bromides investigated indicate that the behavior of the bromides is different from that of the corresponding chlorides. These reactions are also exothermic, but the yields of aldehydes are higher and yields of the ester are lower than those obtained from the acid chlorides. As the alkyl group becomes larger and more branched, the yield of the aldehyde increases. When one goes from acetyl to 2,2-dimethylpropionyl chloride, the yield of aldehyde increases from 5 to 56% and the yield of ester falls from 95 to 33 %. The use of a solvent exerts a profound influence upon the course of the reaction. When the reductions are carried out in 2,3-dimethylbutane, toluene, m-xylene, or methyl acetate, the yield of aldehyde increases at the expense of the ester. A good example of this is the propionyl chloride reaction; the neat reaction affords ester almost exclusively, but, when 2,3-dimethylbutane is employed as a solvent, only a 25% yield of ester is realized. Valeryl chloride gives much the same results; the neat reaction produces 81% of the ester, but the same reaction conducted in 2,3-dimethylbutane gives only 9 %. An important exception to this solvent effect is observed with tri-n-butyltin chloride in which a substantial yield of ester is obtained from propionyl chloride. A reasonable explanation of this is given in the accompanying paper. lo It has been observed that if an aldehyde or a ketone is added to the reaction mixture a “mixed” ester, whose alkoxy fragment is derived from the added carbonyl compound, is formed. For example, the addition of 1 mole of benzaldehyde to a mixture of 1 mole each of propionyl chloride and tri-n-butyltin hydride resulted in a 7 0 x yield of benzyl propionate (eq. 6). Here C2HsCOCI
+ CsHjCHO + Sn*-H + CzHsCHO + C3Hi02CC2Hj+ Sn*-C1
Table 11. Yields of Esters from the Reaction of Acid Chlorides with Tri-n-butyltin Hydride in the Presence of Equimolar Amounts of Carbonyl Compounds at Room Temperature
R’R”C0
Solvent“
Neat CH3 Cyclohexanone Neat G H s Cyclohexanone CsHsCHO Neat CHI Neat CzHj CsHbCHO CHI p-CH,OCeHaCHO Neat DMB C?Hs C6HjCHOb DMB CzHj CsHjCHO (C2HdzO G H j CsHjCHO CEHjCH 3 C2Hs CeHjCHO DMB G H s Cyclopentanone DMB G H 5 n-Heptaldehyde DMB CZHj p-CH3CCH4CHO G H j W Z - C H ~ C ~ H ~ C HDMB O DMB G H s m-ClCsH4CHO CHaCOOCHa C2Hj p-ClCeHdCHO C2H5 p-CHaOCeH4CHO CeHjCHa G H s p-CHaOCsHhCHO (CzHj)zO
-Yield, %-RCOZ- RC02CHzR CHR’R” 31 78 25 10 22
. . .c ...c
. . .c , . ,c . . .c 75
. ..c . . .c . . .c
14
...c . . .c
5 12 23 70 21 63 34 13 35 3.2 22 39 19 39 5.1 13 20
Concentration 0.63 M when solvent was used. DMB = 2,3dimethylbutane. * Trimethyltin hydride was used. Yield not determined. a
(10) E. J. Walsh, Jr. and H. G. Kuivila, J . A m . Chem. SOC.,87, 576 (1965).
+ R-X Sn*-X + R. + Sn*-H --f Sn*. + R-H
Sn*. R.
--f
(7 ) (8)
the reaction of acid chlorides with the hydrides occurs readily in nonpolar solvents, it was thought that a freeradical mechanism may also be involved here. Results obtained in the study of this reaction indicate that this is so. Equations 9-11 comprise our mechanistic
+ Sn*H +Sn*. + QH R&O + Sn*CI Sn* . + RCOCl+ R&O + Sn*H + RCHO + Sn*. Q.
(6)
again the role of solvent is important. When this reaction is conducted in solution (0.63 in either tol-
RCOCl
uene or 2,3-dimethylbutane, only a 3 4 z yield of benzyl propionate is realized. These and other examples are listed in Table 11. Ketones in general appear not to be as reactive in these reactions as aldehydes, When cyclohexanone is added to the neat reaction mixture under the same conditions as in the experiment with benzaldehyde, only a 12 % yield of cyclohexyl propionate is found. Acetone and acetophenone give somewhat smaller yields of “mixed” ester under these same conditions. l i The objective of our work has been to elucidate aspects of the mechanisms of these reactions between acid halides and organotin hydrides. In this paper we shall discuss the mechanism of aldehyde formation, The reactions which lead to esters are discussed in the accompanying paper. Mechanism of Aldehyde Formation. It has recently been demonstrated6 that the reaction between alkyl halides and tri-n-butyltin hydride proceeds by a freeradical chain mechanism probably involving abstraction of the halogen atom by a tin radical, followed by reaction of the alkyl radical with another mole of tin hydride to produce the reduced product and another tin radical (eq. 7 and 8) as chain-carrying steps. Since
(9) (10) (11)
hypothesis for the formation of the aldehyde. In this scheme Q . is some free radical arising from a bimolecular reaction between the hydride and the acid chloride or by other means. This free radical abstracts a hydrogen atom from the organotin hydride molecule producing an organotin free radical, The tin radical can then abstract a chlorine atom from the acid chloride, generating an acyl free radical which can then react with another molecule of organotin hydride to form the aldehyde and another organotin radical. Evidence for this mechanism comes from studies on fragmentation, free radical catalysis, and substituent effects. Fragmentation. Acyl radicals have been shown to be intermediates in vapor phase decompositions of some aldehydes and ketones, and their formation in solution is usually initiated by photolysis or by reaction of aldehydes with alkoxy r a d i c a l ~ . ~ *Two , ~ ~ new methods for generating these radicals have been reported by Bartoni4 and Waters15 and co-workers. These involve photolysis of acyl xanthates and azodibenzoyl compounds, respectively. Probably the most important reaction of acyl radicals is decarbonylation at moder(1 1) As approximated from relative areas of n-propyl propionate and “mixed” ester peaks in gas chromatograms. (12) C. Walling, “Free Radicals in Solution,” John Wiley and Sons, Inc., New York, N. Y . ,pp. 273-285, 325. (13) B. G . Tucker and E. Whittle, Proc. Chem. SOC.,93 (1963). (14) D. H. Barton, e l al., J . A m . Chem. SOC.,84, 1967 (1962). (15) D. MacKay, U. F. Marx, and W. A. Waters, J . Chem. Soc., 4793 ( 1964).
Journal of the American Chemical Society / 88:3 / February 5, 1966
ately high ternperatures.'*J6 They can therefore be used as intermediates in the formation of alkyl radicals (eq. 12). Furthermore, the formation of carbon A
R&=O
-+
R.
+ CO
(12)
monoxide may be taken to indicate the intermediacy of acyl radicals. Decarbonylation cannot compete with reaction 11 in most cases because tri-n-butyltin hydride is highly efficient as a hydrogen donor. In order to foster the competition we sought to use an acid chloride which would decarbonylate with relative ease, i.e., one which would yield a particularly stable alkyl radical. Triphenylacetyl chloride was selected. Numerous attempts were made by mixing the acid chloride and hydride in xylene and heating the reaction mixture to 100-110" in a system attached to a gas buret. In every case the amount of gas collected was too small to give a good infrared spectrum. However, if the hydride was added slowly, thereby limiting its availability, enough carbon monoxide (10-12 %) was collected to give the characteristic infrared spectrum. l7 A 5 % yield of triphenylmethane was isolated along with a 90% yield of triphenylacetaldehyde; eq. 13-16 account for these results.
+ Sn*Cl (CsH&CCHO + Sn*. (CsHj)aC&O + Sn*H (CsH&CC:=O + (CeH&C* + co (CsH5)sC. + Sn*H + (C&)ICH + Sn*.
(C6H&CCOCl+ Sn*. +(CsH&Cd=O --f
(13) (14) (15) (16)
A control experiment was run on the same scale under the same conditions as the experiment above with tri-nbutyltin chloride and the acid chloride to test whether the chloride is a strong enough Lewis acid to generate the acylium ion which might decarbonylate to give the triphenylcarbonium ion which, in turn, would be expected to react with the hydride. There was no evolution of carbon monoxide. Another type of fragmentation was observed in the reduction of benzyl chloroformate. The benzoyloxycarbonyl free-radical intermediate apparently dissociates rapidly, even at room temperature, to carbon dioxide and the more stable benzyl radical. The benzyl radical then reacts with the hydride to produce toluene as shown in eq. 17-20. Gas chromatographic
+
C O H ~ C H ~ O C O C Sn*. ~
--f
CeH5CH20&0
+ Sn*Cl
+ COZ CsHsCH20&0 + Sn*H +CeH5CH20CH0+ Sn*. CsH5CH2 + Sn*H --f C6H5CH3+ Sn* . CEH~CH~OC=O-+- CBHbCHz.
e
butyltin hydride yielded only ethyl formate i n d no indication of carbon monoxide or ethane. Presumably the energy of activation for decarboxylation of the ethoxycarbonyl radical is sufficiently high that reaction with the hydride is its exclusive fate under the conditions used. Free-Radical Catalysis. Ethyl chloroformate reacts very slowly at 80" with tri-n-butyltin hydride, so it served as a particularly good substrate for catalysis experiments. The reaction with tri-n-butyltin hydride was found to be subject to free-radical catalysis as is shown by the observation that ethyl chloroformate undergoes only 5 % reduction in 3 hr. at 80", whereas the reaction is complete under the same conditions in the presence of 1.6 mole % of azobisisobutyronitrile (see Table 111). The products in each case were ethyl formate and tri-n-butyltin chloride.
(17) (18) (19) (20)
analysis indicated a 39% yield of toluene and a 61 yield of benzyl formate. This type of free-radical fragmentation was observed by Thynne and Gray1* with the methoxycarbonyl free radical. This intermediate, at the temperature used, 120-1 85 ", breaks down quantitatively to the methyl radical and carbon dioxide (eq. 21-24). On (16) See, e.g., V. P. Grim, et al., J . Org. Chem., 28, 2643 (1963); w. A. Banner and F. D. Mango, ibid., 29, 29 (1964); D. Schuster and J. D. Roberts, ibid., 27, 51 (1962); J. W. Wilt and A. A. Levin, ibid., 27, 2319 (1962). (17) R. H. Pierson, A. N. Fletcher, and E. St. C. Gantz, Anal. Chem., 28, 1218 (1956). (18) J. C. J. Thynne and P. Gray, Proc. Chem. SOC.,141, 295 (1962); Trans. Faraday SOC.,58, 2403 (1962).
Kuivila, Walsh
Table 111. Catalyzed and Uncatalyzed Reaction of Ethyl Chloroformate with Tri-n-butyltin Hydride at 80 O Time, hr. 0.5 1.5 3.0 18.5 1.6 mole
Catalyzeda
--
completed Uncatalyzed
30 98-100 100
0 2-4 5 35
of azobisisobutyronitrile.
A brief examination of the reduction of benzoyl chloride provided less clear-cut results. In experiments similar to those described above, the half-life of the uncatalyzed reaction was roughly twice that of the catalyzed reaction. However, the result was complicated by the observation that the catalyzed reaction produced 30 % of ester while the uncatalyzed reaction produced only 13%. A detailed explanation of these results will not be attempted here, but, as is shown in the accompanying paper,I0 there seem to be at least two competing mechanisms for ester formation. This fact can complicate the problem of product distribution under varying conditions. Relative Reactivities of Acid Chlorides. The relative reactivities of acid chlorides were determined by allowing each acid chloride to compete with a benzyl bromide or 2-bromooctane for a deficiency of tri-n-butyltin hydride at 25". The reaction product was analyzed by gas chromatography using an internal standard. Satisfactory determinations of aldehyde and acid chloride concentrations could not be obtained, but that of the hydrocarbon produced from the alkyl halide could. The amount of acid chloride was then determined by difference assuming no wastage of the organotin hydride. Relative rate constants were computed by the method of Ingold and Stow.'g The fact that electron-withdrawing groups facilitate the reaction rules out an acylium ion mechanism, (19) C. K. Ingold and F. R. Stow, J. Chem. SOC.,2918 (1927).
I Aldehyde Formation in Acyl Halide-Organotin Hydride Reactions
574 Table IV. Relative Reactivities of Acyl Halides toward Tri-n-butyltin Hydride at 25" in Solution (0.63 M)a Acyl halide
0.50
i 5 Y
- 1.00
As determined by competition with sec-octyl bromide for an insufficient amount of the hydride. * o-Dichlorobenzene,
-Y
o
1.00
- 0.50
0.50
- 1.00
0
0.40 0.60 0.80
0.20
U.
Figure 1. Hammet plots for the reaction of substituted benzoyl chlorides with the tri-iz-butyltin radical.
(eq. 25 and 26). Reaction 25 would be facilitated by electron-releasing substitutents. RCOCl RC+=O
+ Sn*+ RC+=O + Sn*C1 + Sn*H +RCHO + SN*+ ---f
(25) (26)
The results are consistent with the free-radical mechanism postulated with reaction 10 subject to substantial polar effects as depicted by the contributing structures in I or the shorthand representation 11. The electro-
[
(Ar-i-Cl
Sn*
I
L
o
I1
J
positive organotin radical functions as an electron donor to the electronegative chlorocarbonyl group. The carbonyl group assumes a degree of carbanionic character which is novel for reactions leading to the formation of the acyl radical. In much of the previous work, the source of the acyl radical has been the reaction of an aldehyde with an electrophilic species, such as the benzoyloxy radicaL20 In such cases the acyl carbon assumes acylium ion character in the transition state, structure 111.
[ o Ph-c..
61.40 38.10 9.50 8.20 2.34 1.27 1.00 0.937 0.290 0.166 331 28.78 2.07 5.63
42.20
9.70
5.56 1.00
2.92 1.00
0.116
0.084
0.660 0.540 0.430 0.373 0.337 0.227 0 -0.069 -0.170 -0,268
I
1
-0.20
U
- 0.50
1.50
I
rate inMeOAc DCBb
Benzoyl chloride p-Cyano p-Trifluoromethyl m-Trifluoromethyl m-Chloro rn-Fluoro g-Chloro H m-Methyl p-Methyl p-Methoxy Benzoyl bromide Benzyl bromide sec-Octyl bromide Propionyl chloride
tn
s
-Relative m-Xylene
. . H e...O-
+
i -ph
are 0.963 and 0.955, respectively. Corresponding values of p are 2.61 and 2.02, respectively. The effect of solvent on the Hammett correlation has been studied briefly. It can be seen from Table I V and Figure 1 that the nature of the solvent can exert a profound effect. The p value in methyl acetate (4.0) is considerably greater than that in m-xylene or odichlorobenzene (2.7). Two effects could be operable here. One, proposed by Howard and Ingold,21would be due to the polarizability or dielectric constant of the solvent, an increase in which would tend to stabilize a charged transition state and thereby increase the p value. This is not the explanation for the solvent effect here, because, although methyl acetate has a higher dielectric constant (6.68) than m-xylene (2.37), o-dichlorobenzene has an even higher dielectric constant of 9.93 and substituent effects in this solvent are similar to those obtained in m-xylene. The other effect may be a specific solvent effect which is not unknown in free-radical chemistry.22 We do not feel, however, that we can describe this effect in our system with any certainty on the basis of the three solvents used. The results of other competitive experiments listed in Table IV show a much greater reactivity of benzoyl bromide than benzoyl chloride as would be expected from a consideration of the respective bond dissociation energies, An interesting result is the greater reactivity of propionyl chloride over benzoyl chloride. From the polar effects in the reduction of benzoyl chlorides this may seem surprising. However, the aromatic nucleus can often function as an electron-releasing seat of unsaturation, structure IV. The relative reactivity of the benzoyl halides would be
1'
111
The Hammett correlation appears to be better with r than with U-. Values of r, the correlation coefficient, (20) C. Walling and E. McElhill, J . Am. Chem. SOC.,73, 2927 (1951).
(21) J. A. Howard and I
